Summary Specific Aim 1: Study the diagnostic accuracy of stress CT perfusion CT scanners can acquire high quality images of the coronary arteries. CT coronary angiography has high diagnostic accuracy in the great majority of patients but may not have sufficient resolution or image quality to assess the patency of coronary stents and heavily calcified vessels. Using CT to image stress myocardial perfusion could help solve the diagnostic uncertainty in those special subsets of patients. In addition, while high resolution overall, the resolution of a CT scan for grading the severity of a coronary stenosis in a 3 mm artery can be marginal. Therefore, another area where CT stress perfusion could provide the physiologic assessments needed to help determine whether an anatomic stenosis is severe enough to have caused ischemia or warrant intervention. To address these issues, we have studied 58 patients as part of the multicenter Core320 study which compares CT coronary angiography and stress CT perfusion with conventional quantitative invasive coronary angiography and SPECT perfusion. We were the leading North American recruitment site for this study which recently closed enrollment. Additionally, we are leading an ancillary study that includes comparison of CT perfusion with stress MRI perfusion. That ancillary study is under analysis. Specific Aim 2: Develop low dose cardiac CT imaging protocols that retain high diagnostic accuracy. Another pressing research direction has been developing low radiation dose CT scans of the heart. The public and academic medical communities have both realized that radiation exposure from diagnostic imaging is increasing at a rapid pace and may be associated with some health risks. Thus, finding methods for reducing radiation exposure in CT scans of the heart is a significant priority. To the best of our knowledge, the NHLBI cardiac CT program has the lowest average radiation exposure of any site using the 320 detector CT scanner. We are leading investigations to improve the technology and create even lower dose CT imaging protocols. Specific Aim 3: Develop CT planning methods for structural heart disease interventions. New techniques to introduce large implants into the aorta for transcatheter aortic valve replacement and related procedures have been developed at NHLBI. CT can be used to plan these complex procedures which can be lifesaving. NHLBI serves as the CT Core Lab for a large multicenter trial of 100 patients to evaluate the safety and efficacy of this technique throughout the USA. Specific Aim 4: Provide safe and accurate cardiovascular phenotyping for other NIH . In conjunction with other investigators from not only the Cardiology Branch, but also NHLBI and other institutes, the Laboratory of Cardiovascular CT provides expertise in performing and interpreting cardiovascular exams. This data provides valuable information on the cardiac and vascular pathophysiology of mutiple systemic and rare genetic diseases.